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Modulation of fluoroaluminate‐induced inositol phosphate formation by increases in tissue cyclic AMP content in bovine tracheal smooth muscle
Author(s) -
Hall I.P.,
Donaldson J.,
Hill S.J.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb15861.x
Subject(s) - medicine , endocrinology , forskolin , inositol phosphate , inositol , isoprenaline , chemistry , calcium , biology , receptor , stimulation
1 The effect of fluoroaluminate complexes (AlCl 3 plus NaF) upon smooth muscle tone, [ 3 H]‐inositol phosphate accumulation and [ 3 H]‐cyclic AMP accumulation has been investigated in slices of bovine tracheal smooth muscle. 2 Fluoroaluminate (10 μ m AlCl 3 + various concentrations of NaF) elicited concentration‐dependent contractions of bovine tracheal smooth muscle strips at concentrations of NaF in the range 1–10 m m . The resultant contractile response was reversed by isoprenaline (50 n m ) and was preserved in calcium‐free medium. 3 Fluoroaluminate stimulated [ 3 H]‐inositol phosphate formation at concentrations of NaF over 1 m m . The response to 20 m m NaF + 10 μ m AlCl 3 was 164 ± 29% of the response to 1 m m histamine. Fluoroaluminate also increased the incorporation of [ 3 H]‐ myo ‐inositol into membrane phospholipids. 4 Fluoroaluminate produced a small rise in [ 3 H]‐cyclic AMP levels (2.1 fold increase over basal with 20 m m NaF). The response to forskolin (1 μ m , 8.6 fold over basal) was reduced by fluoroaluminate in a concentration‐dependent manner, but still remained significantly ( P < 0.05) elevated over the response to fluoroaluminate alone. 5 The [ 3 H]‐inositol phosphate response to fluoroaluminate was inhibited by salbutamol (maximum inhibition 60%, IC 50 = 0.08 μ m ), forskolin (1 μ m , 46% inhibition) and isobutylmethylxanthine (1 m m , 73% inhibition). 6 These data suggest that inhibition of agonist‐induced inositol phospholipid turnover by cyclic AMP in this tissue can occur at the post‐receptor level.